- Korea Research Institute of Bioscience and Biotechnology identifies role of NMUR2 protein in driving glioblastoma growth

- Candidate compound shows enhanced anticancer effect when combined with standard drug, raising hopes of overcoming resistance and relapse

Researchers at the Korea Research Institute of Bioscience and Biotechnology conduct experiments on a protein that suppresses glioblastoma growth. [Korea Research Institute of Bioscience and Biotechnology]
Researchers at the Korea Research Institute of Bioscience and Biotechnology conduct experiments on a protein that suppresses glioblastoma growth. [Korea Research Institute of Bioscience and Biotechnology]

South Korean researchers have identified a new treatment strategy to suppress the growth of glioblastoma, a notoriously difficult-to-treat brain cancer with a high rate of recurrence.

The Korea Research Institute of Bioscience and Biotechnology announced Tuesday that a research team led by Han Tae-su at its Biotech New Drug Translational Research Center had identified the mechanism behind NMUR2, a key protein that drives malignant proliferation in glioblastoma, and discovered a candidate compound capable of blocking it.

Glioblastoma is one of the most aggressive malignant brain tumors, characterized by rapid progression and frequent recurrence. The standard chemotherapy drug temozolomide, or TMZ, is currently used to treat the disease, but more than half of patients develop drug resistance, severely limiting treatment options.

The research team analyzed tissue data from brain cancer patients and confirmed that NMUR2 protein is expressed at abnormally high levels in cancerous tissue compared with normal brain tissue. NMUR2 expression also increased in proportion to the malignancy of the tumor.

An AI-generated image illustrating the identification of NMUR2 as a new treatment target in glioma and the discovery of inhibitor candidate compounds. [Korea Research Institute of Bioscience and Biotechnology]
An AI-generated image illustrating the identification of NMUR2 as a new treatment target in glioma and the discovery of inhibitor candidate compounds. [Korea Research Institute of Bioscience and Biotechnology]

In cancer cells, artificially increasing NMUR2 levels accelerated cell proliferation and migration. Conversely, reducing the protein's expression significantly decreased cancer cell proliferation.

The research team also found that NMUR2 triggers the release of calcium ions inside cancer cells and activates the STAT5 protein, which in turn switches on PIM1 and FOXM1 — genes involved in cell division. NMUR2 effectively acts as an ignition switch, continuously sending growth commands to cancer cells.

To find a drug that could block this switch, the team screened 6,331 compounds. They identified a candidate called NNC 05-2090 that binds to NMUR2 and blocks its signaling.

When administered to glioblastoma cells and a mouse model of brain cancer, the compound suppressed cancer cell proliferation and reduced tumor size.

When used in combination with temozolomide, the treatment produced a stronger anticancer effect than either agent alone, pointing to a potential new combination therapy that could address the limitations of current treatments.

The research team led by Han Tae-su (right) that conducted the study. [Korea Research Institute of Bioscience and Biotechnology]
The research team led by Han Tae-su (right) that conducted the study. [Korea Research Institute of Bioscience and Biotechnology]

The study stands out because it targets NMUR2 itself — the upstream transmitter of growth signals — rather than blocking individual steps in the cancer cell division process. Cutting off multiple cancer growth signals at once, the approach is expected to contribute to the development of new targeted anticancer drugs.

Further research is needed, however, before the findings can be applied to actual patients. The study is currently at an early preclinical stage, with efficacy confirmed only in cell and animal experiments. Researchers still need to verify the candidate compound's ability to cross the blood-brain barrier, its stability in the body, and its safety under long-term administration.

"This is a meaningful achievement in that we identified a new cause of malignant proliferation in glioblastoma and validated the potential of a drug to control it," Han said. "If we can improve the compound's ability to penetrate the blood-brain barrier and refine the drug delivery system, this could lead to the development of an innovative new drug applicable to brain cancer patients."

The findings were published in the International Journal of Biological Sciences.


nbgkoo@heraldcorp.com